Comparison of Clinical Effects of Azathioprine and Rituximab NMO-SD Patients

September 29, 2020 updated by: Vahid Shaygannejad, Isfahan University of Medical Sciences

Comparison of Annual Relapse Rate, Expanded Disability Status Scale, and Side Effects Between Azathioprine and Rituximab in Patients With Neuromyelitis Optica Spectrum Disorders

The purpose of this study is to compare annual relapse rate, expanded disability status scale, and side effects of azathioprine and rituximab in patients with neuromyelitis optica spectrum disorder during a one year follow up through a randomized clinical trial.

Study Overview

Status

Completed

Detailed Description

Neuromyelitis Optica Spectrum Disorder (NMO-SD) is a recurrent inflammatory demyelinating disease affecting the central nervous system. The disease is clinically recognized by optic neuritis and transverse myelitis and is associated with high risk of mortality. Each attack worsens patients' disability. This means that after 5 years of the disease onset, half of patients need to use wheelchair and approximately 50% of them become blind.

Considering that the disease can be disabling for patients, the maintenance treatment should be applied in addition to treatment of acute attacks, in order to prevent future recurrences. Acute attacks are usually treated with high doses of intravenous corticosteroids. Plasmapheresis is also used when patients fail to response to corticosteroids. B lymphocyte inhibitors are used as the maintenance therapy in these patients. First line therapeutic medications include azathioprine and rituximab which are being recommended for long term therapy and second line medications include methotrexate and mycophenolate mofetil.

Azathioprine is an immune-modulatory agent which is available in the oral form and don't require hospitalization to be administered, however, because of side effects such as bone marrow suppression and hepatotoxicity, periodic check of blood cells and liver enzymes are needed. Rituximab is a cluster of differentiation antigen 20 inhibitor which leads to decreased B lymphocytes and antibody in patients. This medication is only available in the injectable form and needs hospitalization to be administered. Close monitory is needed during the administration considering severe side effects such as allergic reactions and respiratory distress. However, laboratory tests are not needed in patients taking rituximab although it is more expensive than azathioprine. No clinical trial has been performed previously to compare clinical efficacy of these two drugs in NMO-SD patients. Therefore, we aimed to compare their efficacy through a randomized clinical trial.

Study Type

Interventional

Enrollment (Actual)

86

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 48 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of neuromyelitis optica spectrum disorder based on the recent guidelines in 2015
  • Expanded disability status scale between 0 and 7
  • Age between 18 and 50 years old

Exclusion Criteria:

  • Pregnancy or lactation during the study
  • Deciding to leave the study by patient
  • Lack of consent to enter the study
  • Lack of cooperation for follow up
  • Severe side effect of the medication
  • Treatment with other immunosuppressant medications (including but not limited to cyclophosphamide, mycophenolate mofetil, methotrexate, others) within two months before intervention
  • Taking any other immunosuppressant or other type of medication (including herbal drugs) without permission of the physician during the study.
  • Presence of other autoimmune disease (including but not limited to Behcet disease, systemic lupus erythematosus, rheumatoid arthritis, and others)
  • Presence of liver disorders
  • Presence of hematologic disorders
  • Presence of heart failure
  • Receipt of a live vaccine within 4 weeks prior to intervention
  • Previous treatment with Azathioporine or Rituximab
  • History of HIV, hepatitis B, or hepatitis C
  • Ongoing daily steroid use
  • History of severe allergic or anaphylactic reaction to monoclonal antibodies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Azathioprine
Patients in this group will receive 50 mg of azathioprine, two times each day and gradually increased to maximum dose of 3 g daily with the aim of lymphocytes count less than 1500.
Patients are started with Azathioprine 50 mg tablets, taken orally twice a day. The medication dose is increased gradually with the aim of lymphocytes count bellow 1500 and to the maximum dose of 3 g Azathioprine per day. Cell blood count is checked once a week in the first month of treatment, once every two weeks in the second month of treatment, and monthly in the third month of treatment to make decision about medication dose.
Other Names:
  • Azathioprine Mehrdaru®
Experimental: Rituximab
Patients in this group will receive 1g of Rituximab in 500 cc normal saline serum through intravenous infusion with two weeks intervals (as one course) and each course of treatment is repeated every 6 months.
Patients will receive 1 g of Rituximab (two vials of RediTux 500 mg/50 ml) in 500 cc normal saline serum through intravenous infusion and this will be repeated two weeks later. This cycle will be repeated every 6 months.
Other Names:
  • RediTux®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annual Relapse Rate
Time Frame: one year
annual relapse rate will be measured in the baseline (according to patients' history in the last year) and after 12 months of intervention.
one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expanded Disability Status Scale
Time Frame: one year

expanded disability status scale will be measured in the baseline and after 12 months of intervention.

Expanded disability status scale (EDSS) is a measure of disability for patients. The score ranges from 0-10, with 0 showing normal neurological exam and 10 showing death due to the disabling disease. Thus, higher scores represent more profound levels of disability.

one year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Drug Reactions
Time Frame: one year
adverse drug reactions will be observed closely and reported during the intervention. We will compare the number of adverse drug reactions in two groups. Also, adverse drug reactions will be described by details in each group.
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Vahid Shaygannejad, M.D., Department of Neurology, School of Medicine, Isfahan University of Medical Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (Actual)

November 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

December 21, 2016

First Submitted That Met QC Criteria

December 22, 2016

First Posted (Estimate)

December 23, 2016

Study Record Updates

Last Update Posted (Actual)

September 30, 2020

Last Update Submitted That Met QC Criteria

September 29, 2020

Last Verified

September 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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